AIMS: Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter m
ethylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. MATERIALS AND METHODS: In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. RESULTS: The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. CONCLUSION: Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy.
After denervation, mRNA levels of the jun and fos protooncogenes and of the muscular differentiation factors myoD1 and myogenin are increased. Here, immunohistochemistry was used (a) to show that this increase in mRNA is followed by an increase in the transcription factor proteins, and (b) to deter
mine which cell populations in skeletal muscle express these factors after denervation. Rat diaphragms were denervated and analyzed after periods of 90 min-8 days. An increase in Fos and Jun as well as MyoD1 and Myogenin immunoreactivity was found after 2-2.5 days of denervation. Fos, MyoD1, and Myogenin immunoreactivity was mostly confined to muscle cell nuclei, whereas Jun antibodies stained muscle cell and some interstitial cell nuclei. A selective expression of any of the four transcription factors in muscle cell nuclei closely associated with motor endplates could not be detected in either denervated or innervated muscle at any time point examined, indicating that synaptic and extrasynaptic muscle cell nuclei are activated simultaneously after denervation. These results suggest that a genetic program which includes protooncogenes and myogenic differentiation factors is activated in skeletal muscle after denervation.